US9195042B2 - Laser based apparatus, methods and applications - Google Patents
Laser based apparatus, methods and applications Download PDFInfo
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- US9195042B2 US9195042B2 US14/348,748 US201214348748A US9195042B2 US 9195042 B2 US9195042 B2 US 9195042B2 US 201214348748 A US201214348748 A US 201214348748A US 9195042 B2 US9195042 B2 US 9195042B2
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B21/00—Microscopes
- G02B21/06—Means for illuminating specimens
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/65—Raman scattering
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/65—Raman scattering
- G01N2021/653—Coherent methods [CARS]
Definitions
- CRS microscopy with contrast from coherent anti-Stokes Raman scattering (CARS) or stimulated Raman scattering (SRS), allows label-free imaging of biological samples with endogenous image contrast based on vibrational spectroscopy.
- CARS coherent anti-Stokes Raman scattering
- SRS stimulated Raman scattering
- embodiments may include fiber-delivered two-color picosecond sources for CARS imaging.
- an 817-nm pump pulse is generated by nonlinear spectral compression of a negatively prechirped pulse from a femtosecond Ti:S (i.e., titanium:sapphire) laser in a 2 ⁇ 2 fiber coupler.
- a femtosecond Ti:S i.e., titanium:sapphire
- the spectrum of the pulse can be compressed by nonlinear propagation in an optical fiber.
- Such a nonlinear spectral compression process retains the optical power in the original pulse, in contrast with spectral filtering.
- a 7.6 nm spectral bandwidth of the femtosecond Ti:S output is compressed to 0.68 nm, which is well-suited for CRS imaging.
- Prechirping of the pulse is accomplished through a rotating cylindrical lens system, which offers tunable dispersion with spatial beam stability, a desirable feature for coupling light into fibers.
- a 1064-nm Stokes pulse is generated by a synchronized, all-fiber time-lens source, and also propagates through the 2 ⁇ 2 fiber coupler. This particular embodiment provides for CARS imaging of mouse skin at a CH 2 stretching frequency (2845 cm ⁇ 1 ) to demonstrate the practicality of the two-color picosecond source.
- this particular embodiment describes an apparatus for coherent anti-Stokes Raman spectroscopy comprising a femtosecond Ti:S laser, a prechirping system, a fiber coupler, and an all-fiber time-lens source synchronized with the femtosecond Ti:S laser and coupled to the fiber coupler.
- Also described within the context of the forgoing apparatus in accordance with the particular embodiment is a method for coherent anti-Stokes Raman spectroscopy imaging comprising: (1) generating a wavelength tunable picosecond pump by nonlinear spectral compression of a prechirped femtosecond pulse from a mode-locked titanium:sapphire laser; (2) generating a picosecond Stokes pulse using an all-fiber time-lens source that is synchronized to the titanium:sapphire laser; (3) combining the pump and Stokes beams in an optical fiber coupler; (4) delivering the combined beams to a sample; and (5) collecting the Raman signal.
- a particular optical apparatus in accordance with the embodiments includes a first laser source that provides a first laser output through a first laser output port.
- This particular optical apparatus also includes a prechirping apparatus optically coupled to the first laser output port to provide a prechirped first laser output from the first laser output.
- This particular optical apparatus also includes a second light source synchronized with the first laser source and having a second light output that is optically coupled (i.e., combined) with the prechirped first laser output, where the second light source is selected from the group consisting of: (1) a second laser source different than the first laser source; and (2) a time-lens source.
- Another particular optical apparatus in accordance with the embodiments includes a laser source that provides a laser output through a laser output port.
- This other particular optical apparatus also includes a prechirping apparatus optically coupled to the laser output port to provide a prechirped laser output from the laser output.
- This other particular optical apparatus also includes a time-lens source synchronized with the laser source and having a time-lens output that is optically coupled (i.e., combined) with the prechirped laser output.
- Another particular optical apparatus in accordance with the embodiments includes a titanium:sapphire femtosecond laser source that provides a laser output through a laser output port.
- This other particular optical apparatus also includes a prechirping apparatus optically coupled to the laser output port to provide a prechirped laser output from the laser output.
- This other particular optical apparatus also includes an all-fiber time-lens source synchronized with the titanium:sapphire laser source and having a time-lens output that is optically coupled (i.e., combined) with the prechirped laser output.
- a particular imaging method in accordance with the embodiments includes providing an imaging apparatus comprising: (1) a laser source that provides a laser output through a laser output port; (2) a prechirping apparatus optically coupled to the laser output port to provide a prechirped laser output from the laser output; (3) a time-lens source synchronized with the laser source and having a time-lens output that is optically coupled (i.e., combined) with the prechirped laser output; and (4) a microscope coupled with the time-lens output and the prechirped laser output (i.e., as a specimen illumination source).
- This particular imaging method also includes energizing the laser source and the time-lens source while imaging (i.e., Raman imaging) a specimen while using the microscope.
- Another particular imaging method in accordance with the embodiments includes generating a wavelength tunable picosecond pump by nonlinear spectral compression of a prechirped femtosecond pulse from a mode-locked titanium:sapphire laser.
- This other particular imaging method also includes generating a picosecond Stokes pulse using an all-fiber time-lens source that is synchronized to the titanium:sapphire laser.
- This other particular imaging method also includes combining the pump and Stokes beams in an optical fiber coupler.
- This other particular imaging method also includes delivering the combined beams to a sample.
- This other particular imaging method also includes collecting a Raman signal from the sample.
- FIG. 1 shows an experimental configuration of a of a fiber-delivered two-color picosecond source for CARS imaging in accordance with a first embodiment.
- a 1064-nm synchronized all-fiber time-lens source is described in detail in Wang et al., “Synchronized time-lens source for coherent Raman scattering microscopy,” Opt. Express 18, 24019-24024 (2010), and is incorporated herein fully by reference.
- M mirror
- G 1800 line/mm grating
- BS beam splitter
- HWP half-wave plate
- QWP quarter-wave plate
- L2 aspheric lens
- CFBG chirped fiber Bragg grating
- L3 collimating lens
- LPF 800 nm long pass filter
- PC polarization controller.
- FIG. 2 shows for the first embodiment: (a) Measured (dots) and calculated (line) pulse width as a function of rotation angle of a cylindrical lens. (b) Measured 817-nm pump pulse spectra at various output powers from a fiber coupler. (c) Measured second-order interferometric autocorrelation trace at 150 mW output power.
- FIG. 3 shows for the first embodiment: (a) Measured spectrum of a time-lens output. Cross correlation traces of the time-lens output with an 87-fs pulse. (b) and the 150-mW, 1.8-ps pulse from the fiber coupler (c). Inset in (c) shows the measured sum-frequency signal at the half maximum of the cross-correlation trace over 180 seconds.
- FIG. 4 shows for the first embodiment a CARS image of sebaceous glands at the CH 2 stretching frequency in a mouse ear. 512 ⁇ 512 pixels, 4 s/frame, no average.
- FIG. 5 shows an experimental configuration of a fiber-delivered two-color picosecond source for CARS imaging in accordance with a second embodiment.
- M mirror
- G 1800 line/mm grating
- L1:f 30 cm collimating lens
- BS beam splitter
- HWP half-wave plate
- QWP quarter-wave plate
- L2 aspheric lens
- CFBG chirped fiber Bragg grating
- L3 collimating lens
- LPF 800 nm long pass filter
- PC polarization controller
- BB broadband
- MZ Mach-Zehnder intensity modulator. Electrical paths are labeled with dashed lines, and optical paths are labeled with solid lines.
- FIG. 6 shows for the second embodiment: (a) Measured 817-nm pump spectra from the WDM at linear propagation (dashed line) and maximum spectral compression (solid line). (b) Cross correlation trace between the 90-fs and the spectrally compressed 817 nm pulses.
- FIG. 7 shows for the second embodiment: (a) The measured 1064-nm pulse spectra at various output power from the WDM. Cross correlation trace between the 186-mW 1064-nm pulse with the 90-fs 817-nm pulse from the Ti:S laser (b) and the spectrally compressed 2.7-ps 817-nm pump pulse (c). Inset in (c) shows the measured sum-frequency signal at the half maximum of the cross-correlation trace over 160 s.
- FIG. 8 shows for the second embodiment a CARS image of sebaceous glands at the CH 2 stretching frequency in mouse ear. 512 ⁇ 512 pixels, 4 s/frame, no average.
- a first embodiment is directed towards a fiber-delivered two-color picosecond source for CARS imaging.
- An 817-nm pump pulse is generated by nonlinear spectral compression of a negatively prechirped pulse from a femtosecond Ti:S laser in a 2 ⁇ 2 fiber coupler.
- the spectrum of the pulse can be compressed by nonlinear propagation in an optical fiber.
- Such a nonlinear spectral compression process retains the optical power in the original pulse, in contrast to spectral filtering.
- a 7.6 nm spectral bandwidth of a femtosecond Ti:S output is compressed to 0.68 nm, which is well-suited for CRS imaging.
- Prechirping of the pulse is accomplished through a rotating cylindrical lens system, which offers tunable dispersion with spatial beam stability, a desirable feature for coupling light into fibers.
- a 1064-nm Stokes pulse is generated by a synchronized, all-fiber time-lens source, and also propagates through the 2 ⁇ 2 fiber coupler.
- the first embodiment describes CARS imaging of mouse skin at the CH 2 stretching frequency (2845 cm ⁇ 1 ) to demonstrate the practicality of the two-color picoseconds source in accordance with the embodiments.
- 817-nm femtosecond pulses are generated from a mode-locked Ti:S laser (Tsunami, Spectra-Physics).
- the cylindrical lens is mounted on a rotation stage for rotation in the plane perpendicular to the direction of light propagation.
- the calculated maximum anomalous dispersion is ⁇ 1.4 ⁇ 10e5 fs 2 .
- the prechirped 817-nm pulse is coupled into a 2 ⁇ 2 fiber coupler (FC1064-50B-FC, Thorlabs) for nonlinear spectral compression and fiber-optic beam combining.
- the total propagation length of the 817-nm pump pulse in the fiber is 107 cm.
- a half-wave plate and a quarter-wave plate are inserted before the coupling lens, to adjust the polarization of the output pump pulse after the fiber.
- the 1064-nm Stokes pulse is generated by an all-fiber time-lens source synchronized to the Ti:S laser, which is described in detail in Wang et al., “Synchronized time-lens source for coherent Raman scattering microscopy,” Opt. Express 18, 24019-24024 (2010), and which is incorporated herein fully by reference.
- the RF signal for synchronization is provided by a high-speed photodiode that samples the 80-MHz Ti:S optical pulse train.
- a chirped fiber Bragg grating (CFBG) spliced to the fiber coupler was used as an all-fiber dispersion compensator for the time-lens source.
- a polarization controller (PC) is used to adjust the polarization of the 1064-nm output from the fiber coupler, ensuring that the Stokes pulse is linearly polarized and parallel to that of the pump to maximize CARS signal.
- a discrete RF delay (PDL-10A, Colby Instruments) and a continuously tunable RF delay provide a large tuning range (0.795 ns) to adjust the relative time delay between the pump and the Stokes pulses without any mechanical optical delay line.
- the 2 ⁇ 2 fiber coupler acts as a spatial beam combiner and delivery fiber for both the pump and the Stokes pulses, ensuring perfect spatial overlap of the two beams for CRS imaging.
- the spatially and temporally overlapping pump and Stokes pulses are sent into a microscope (described in detail in Balu et al, “Fiber delivered probe for efficient CARS imaging of tissues,” Opt. Express 18, 2380-2388 (2010), and incorporated herein fully by reference), for CARS imaging.
- the pulse width as a function of the rotation angle of the cylindrical lens is measured [dots in FIG. 2( a )], and compared with theoretical calculation [solid line in FIG. 2( a )] by assuming the maximum dispersion of ⁇ 1.4 ⁇ 10e5 fs 2 at 0°.
- Experimental and theoretical results agree well. Note that as the angle decreases (dispersion increases), the pulse width is compressed to its minimum at 76° due to other dispersive elements in the beam path (e.g., an optical isolator) before the cylindrical lens system.
- the cylindrical lens is fixed at maximum dispersion (0°).
- the measured spectra of the 817-nm pulse as a function of the output power from the fiber coupler are shown in FIG. 2( b ).
- the spectrum is progressively compressed, and reaches its minimum of 0.68 nm at 150 mW output power [dotted line in FIG. 2( b )]. This corresponds to 11.2 times spectral compression from that of linear propagation at low power [solid line in FIG. 2( b )].
- the spectrum broadens again [dash-dotted line in FIG.
- the pulse width at maximum spectral compression (i.e., at 150 mW output), deconvolved from the measured second-order interferometric autocorrelation trace [ FIG. 2( c )], is 1.8 ps.
- the measured spectral bandwidth (FWHM) is 1.7 nm [ FIG. 3( a )].
- FWHM spectral bandwidth
- FIG. 3( b ) shows that the pulse width of the time-lens output is 2.2 ps.
- the cross correlation between the time-lens output and the 1.8-ps spectrally compressed 817-nm pulse is shown in FIG. 3( c ).
- the FWHM is 2.9 ps.
- the RMS timing jitter over a measurement time of 180 seconds is 110 fs, only a small fraction of the pulse widths.
- the measured output power of the 1064-nm Stokes pulse is 110 mW.
- FIG. 4 highlights the practicality of the two-color, fiber-delivered picosecond source for CARS imaging. While CRS imaging of the CH 2 bond is demonstrated, the wavelength tunability of the femtosecond Ti:S laser ensures that a wide range of stretching bands can be covered by the two-color source.
- the particular foregoing first embodiment demonstrates a fiber-delivered two-color, picosecond source for CARS imaging.
- a 2 ⁇ 2 fiber coupler spectrally compresses a pump pulse from a mode-locked femtosecond laser, and spatially combines the pump and the Stokes pulses, the latter of which is generated by a synchronized, all-fiber time-lens source.
- the temporal overlap of the two pulses is electronically adjusted without any mechanical optical delay line, greatly facilitating the temporal alignment of the excitation beams for CRS imaging.
- Mouse skin imaging at CH 2 stretching frequency (2845 cm ⁇ 1 ) is performed to demonstrate the practicality of this source.
- the combination of the all-fiber time-lens source and the nonlinear spectral compression of a femtosecond source in an optical fiber has the potential to make CRS imaging easily accessible to any researcher with a wavelength tunable femtosecond source.
- 80-MHz, 90-fs pump pulses centered at 817-nm are generated from a mode-locked Ti:S laser (Tsunami, Spectra-Physics).
- the prechirp of the femtosecond pulse is provided by a rotating cylindrical lens system in a 4f configuration, which provides tunable anomalous dispersion up to ⁇ 1.4 ⁇ 10e5 fs 2 .
- the prechirped 817-nm pulse is coupled into a WDM for nonlinear spectral compression, fiber-optic beam combining, and delivery.
- a fast GaAs photodetector (ET-4000, 10 GHz, EOT) converts the 80-MHz pump pulse train into a synchronized RF pulse train, which is amplified by broadband RF amplifiers and used to drive the MZ intensity modulator.
- the intensity modulator carves a synchronized 80-MHz, 55-ps optical pulse train from a 1064-nm CW laser (QFBGLD-1060-30PM, QPhotonics).
- the preamp and the power amplifier boost the energy of the optical pulse for nonlinear spectral broadening in 100-m SSMF, which replaces the phase modulators in the time-lens setup.
- the spectrally broadened 1064-nm pulse is compressed with an all-fiber dispersion compressor consisting of a circulator and a chirped fiber Bragg grating.
- the output port of the compressor is spliced to the fiber WDM.
- the fiber WDM serves three purposes: (1) combining the pump and the Stokes beams spatially; (2) nonlinear spectral compression of the pump; and (3) fiber delivery of both beams.
- An in-line fiber polarization controller before the WDM adjusts the polarization of the 1064-nm output, ensuring that the Stokes beam is linearly polarized and parallel to that of the pump to maximize the CARS signal.
- An electronic discrete RF delay (PDL-10A, Colby Instruments) and a continuously tunable RF delay provide a large tuning range (0.795 ns) to adjust the relative time delay between the pump and the Stokes pulses without any mechanical optical delay line.
- PPF long-pass filter
- the spatially and temporally overlapping pump and Stokes pulses are sent into a microscope, as described in detail in Kobat et al., Opt. Express 17, 13354 (2009), which is incorporated herein fully by reference, for CARS imaging.
- PMT GaAsP photomultiplier tube
- the temporal profile of the spectrally compressed pump pulse one may measure cross correlation trace between the 90-fs 817-nm pulse and the spectrally compressed pump pulse, through background-free noncollinear sum-frequency (SF) generation in a barium borate (BBO) crystal, shown in FIG. 6( b ).
- the measured FWHM pulse width is 2.7 ps.
- FIG. 7( c ) To characterize the timing jitter, cross correlation of the Stokes pulse and the 2.7-ps spectrally compressed 817-nm pump pulse is performed [ FIG. 7( c )]. All cross correlation measurements use SF generation in the BBO crystal. A bandpass filter placed before the photodiode removes the residual second harmonic of the 817-nm pulse and the 1064-nm Stokes pulse, which guarantees background-free SF measurement in the collinear configuration. The relative delay between the pulses is readily scanned by tuning the electronic RF delay line, instead of a mechanical delay line used for FIG. 6( b ). FIG. 7( b ) shows that the FWHM pulse width of the compressed 1064-nm pulse is 1.9 ps.
- the FWHM of the cross correlation between the 1064-nm pulse and the 2.7-ps spectrally compressed 817-nm pulse is 3.3 ps.
- the RMS timing jitter over a measurement time of 160 s is 180 fs, only a small fraction of the pulse widths.
- FIG. 8 highlights the practicality of the two-color, fiber-delivered picosecond source for CARS imaging. While CRS imaging of the CH 2 bond is demonstrated, the wavelength tunability of the femtosecond Ti:S laser, together with proper adjustment of the grating angle and choice of fast photodetectors responsive to the pump wavelength, ensures that a wide range of stretching bands can be covered by the two-color source. For example, tuning the pump wavelength to 909 nm, one may demonstrate CRS imaging of drug delivery in mouse skin at a polyene stretching frequency (1600 cm ⁇ 1 ).
- Stokes pulse generation through nonlinear spectral broadening in accordance with the second embodiment is simpler and more cost effective to implement.
- High speed phase modulators and relevant RF filter and amplifiers are no longer needed, eliminating the major cost of the time-lens system.
- the timing jitter described herein is larger than that of the time-lens source, and there is some polarization instability over a long imaging session of several hours.
- a long fiber is more susceptible to environmental variations such as temperature fluctuations and mechanical vibrations.
- a fiber-delivered two-color, picosecond source for CARS imaging through nonlinear spectral transformation The pump pulse is generated through nonlinear spectral compression of a prechirped femtosecond pulse, while the Stokes pulse is generated through SPM-induced spectral broadening of a 55-ps pulse and subsequent dispersive compression.
- Spectral compression of the femtosecond pump pulse, beam combining, and fiber delivery are readily accomplished in a fiber WDM.
- the temporal overlap of the two pulses is electronically adjusted without any mechanical optical delay line, greatly facilitating the temporal alignment of the excitation beams for CRS imaging.
- Mouse skin imaging at CH 2 stretching frequency is performed to demonstrate the practicality of this source.
- the nonlinear spectral broadening scheme of the Stokes pulse replaces phase modulation with phase modulators in the time-lens source, which potentially reduces the complexity and cost of the Stokes source for CRS imaging.
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CN104777146B (en) * | 2015-03-30 | 2018-01-30 | 中国电子科技集团公司第三十八研究所 | A kind of all -fiber Raman spectrometer |
CN106546572B (en) * | 2015-12-13 | 2018-06-19 | 中国科学院大连化学物理研究所 | A kind of short wavelength laser chirality Raman spectrometer |
CN111630448A (en) * | 2018-01-23 | 2020-09-04 | 株式会社藤仓 | Filter element, laser device, fiber laser device, filtering method, and method for manufacturing laser device |
CN109490220A (en) * | 2018-11-07 | 2019-03-19 | 河南工业大学 | A kind of large link rod fracture damage on-line detecting system and detection method based on long chirped fiber grating |
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